Sai-Cheong Lee

Clinical correlates of antifungal macrodilution susceptibility test results for non-AIDS patients with severe Candida infections treated with fluconazole.

ABSTRACT Although the clinical correlates of the reference antifungal susceptibility test results in hematogenous and deep-seatedCandida infection are still controversial, we evaluated the clinical correlates of this test in deep-seatedCandida infections in non-AIDS patients. Thirty-two non-AIDS patients with hematogenous or deep-seated Candidainfections were treated with intravenous fluconazole (400 mg a day), and the clinical outcomes were evaluated. Coexisting bacterial infections were treated with appropriate antibiotics, superinfection or reinfection was excluded, inadequate fluconazole therapy was avoided, and essential surgical intervention was performed. The MICs of fluconazole for these 32 Candida isolates were determined according to the M27-A procedure approved by the National Committee on Clinical Laboratory Standards. MICs were interpreted as susceptible (≤8 μg/ml), dose-dependent susceptible (16 to 32 μg/ml), and resistant (≥64 μg/ml) according to the criteria of the M27-A standard. The success rates were 79% (19 of 24; 95% confidence interval [CI], 59 to 93%) in the susceptible category, 66% (4 of 6; 95% CI, 19 to 95%) in the dose-dependent susceptible category, and 0% (0 of 2; 95% CI, 0 to 84%) in the resistant category. We conclude that the clinical correlation of the reference antifungal susceptibility test results is high in hematogenous and deep-seatedCandida infections.

A 5-Year Study of the Seroepidemiology of Klebsiella pneumoniae: High Prevalence of Capsular Serotype K1 in Taiwan and Implication for Vaccine Efficacy

Seroepidemiology of Klebsiella pneumoniae was determined for 1000 nonrepetitive K. pneumoniae isolates collected by a medical center in Taiwan during 1993-1997. Of these, 630 isolates (63%) were from community-acquired infections; the rest were from hospital-acquired infections. The isolates were serotyped according to capsular antigen by countercurrent immunoelectrophoresis. About 77% were typeable. Serotypes K1 and K2 accounted for 21.7% and 9.3% of the isolates, respectively, followed by K57 (5.1%), K54 (4.2%), K21 (3. 3%), and K16 (3%). The frequency of serotype K1 among bacteremic isolates (30.8%) far exceeded that reported by other investigators worldwide. Molecular typing of random K1 isolates by pulsed-field gel electrophoresis revealed several different pulsotypes, suggesting a nonclonal spread. This study indicates that a Klebsiella vaccine developed in Europe is not optimal for use in Taiwan because it does not contain the most predominant serotypes-K1, K54, and K57.

Candida peritonitis due to peptic ulcer perforation: incidence rate, risk factors, prognosis and susceptibility to fluconazole and amphotericin B

Sixty-two cases of peritonitis due to peptic ulcer perforation were diagnosed between January 2000 and December 2000. Of these 62 cases, 23 isolates of Candida in 23 cases (CP) were cultured from peritoneal fluid. Cultures of peritoneal fluid of 10 (BP) of the remaining 39 cases was positive for bacteria only. Cultures of peritoneal fluid of the remaining 29 cases was negative. Comparison of CP, BP and culture-negative cases did not reveal any significant risk factor. Of the 23 Candida isolates, the Candida species and 48-h MICs of fluconazole and amphotericin B (mean, range ug/ml) were C. albicans 18 (0.688, 0.125-1.0; 0.297, 0.031-0.5), C. glabrata 3 (0.542, 0.125-1.0; 0.25, 0.125-0.5), C. tropicalis 1 (0.25; 0.5), C. intermedia 1 (1.0; 0.125) respectively. Mortality rates of CP, BP and culture-negative peritonitis due to infection were 5/23(21.7%), 0/10 and 1/29(3.4%) respectively. Without effective antifungal therapy, the mortality rate of CP was not low.

Fluconazole Disk Diffusion Test with Methylene Blue- and Glucose-Enriched Mueller-Hinton Agar for Determining Susceptibility of Candida Species

ABSTRACT A 25-μg fluconazole disk diffusion test using a Mueller-Hinton agar plate containing 2% glucose and 5 μg of methylene blue/ml (GM-MH) was compared to the macrodilution reference method for 210Candida species. The GM-MH agar plate was read at 24 h. The predictive values of disks with susceptible, intermediate, and resistant results on the GM-MH agar plate at 24 h were 97.1, 56.3, and 76.5%, respectively.

Nosocomial Infections With Ceftazidime-Resistant Pseudomonas aeruginosa : Risk Factors and Outcome

Prospective studies were conducted for nosocomial Pseudomonas aeruginosa infections from February 1, 1994, to October 30, 1995. Of 97 P. aeruginosa isolates from 97 patients, 35 were resistant to ceftazidime. Logistic regression revealed previous cephalosporin or piperacillin use as independent risk factors for nosocomial ceftazidime-resistant P. aeruginosa infection. Pulsed-field gel electrophoresis revealed that four nosocomial ceftazidime-resistant P. aeruginosa infections were caused by cross-infection, probably through medical personnel.

An Outbreak of Methicillin-Resistant Staphylococcus aureus Infections Related to Central Venous Catheters for Hemodialysis

OBJECTIVES To determine risk factors for hemodialysis catheter-related bloodstream infections (HCRBSIs) and investigate whether use of maximal sterile barrier precautions would prevent HCRBSIs. SETTING Tertiary-care medical center hemodialysis unit. DESIGN Open trial with historical comparison and case-control study of risk factors for HCRBSIs. METHODS Prospective surveillance was used to compare HCRBSI rates for 1 year before and after implementation of maximal sterile barrier precautions. A case-control study compared 50 case-patients with HCRBSI with 51 randomly selected control-patients. RESULTS The HCRBSI rate was 1.6% per 100 dialysis runs (CI95, 1.1%-2.3%) in the first year and 0.77% (CI95, 0.5%-1.1%) in the second year (P = .0106). The most frequent cause of HCRBSI was MRSA in the first year (15 of 32) and MSSA in the second year (13 of 18). Ten MRSA blood isolates in the first year were identical by PFGE. Diabetes mellitus was a risk factor for HCRBSI. Age, gender, site of hemodialysis central venous catheter (CVC), other underlying diseases, coma score, APACHE II score, serum albumin level, and cholesterol level were not associated with HCRBSI and did not change between the 2 years. Hospital stay was prolonged for case-patients (32.78 +/- 20.96 days) versus control-patients (22.75 +/- 17.33 days), but mortality did not differ. CONCLUSIONS Use of maximal sterile barrier precautions during the insertion of CVCs reduced HCRBSIs in dialysis patients and seemed cost-effective. Diabetes mellitus was associated with HCRBSI. An outbreak of MRSA in the first year was likely caused by cross-infection via medical personnel.

Risk factors of mortality and comparative in-vitro efficacy of anidulafungin, caspofungin, and micafungin for candidemia

BACKGROUND Although echinocandins have high in vitro antifungal efficacy according to prior reports, comparative studies on the clinical cure rates of anidulafungin, caspofungin, and micafungin in systemic candida infections have not yet been reported. METHODS Interpretation of clinical and microbiological responses to anidulafungin, caspofungin, and micafungin in 109 cases of candidemia was done according to the published criteria. The clinical cure rates between patients treated with echinocandins and patients treated with fluconazole were also compared. The minimal inhibitory concentrations (MICs) of anidulafungin, caspofungin, micafungin, and fluconazole for these 109 blood isolates of candida were determined with the Clinical and Laboratory Standards Institute M27-A reference microdilution method. Logistic regression with forward selection was used to determine the important factors of prognosis with variables such as age, underlying diseases, acute physiology and chronic health evaluation (APACHE) III score, persistent candidemia, and antimicrobial therapy. RESULTS Among the 109 cases of candidemia, 70 were treated with echinocandins, azoles, or amphotericin B for ≥7 days. The clinical cure rate of cases treated with antifungal agents adequately (≥7 days) and inadequately (<7 days) were 44/70 (62.9%) and 4/39 (10.2%), respectively, with significant difference (p < 0.0001). Clinical cure rates of anidulafungin, caspofungin, micafungin, and fluconazole were 18/30 (60.0%), 8/9 (88.9%), 5/7 (71.4%), and 9/18 (50%), respectively. The difference in APACHE III score between treatment success and failure cases was significant. The MIC50/MIC90 of anidulafungin, caspofungin, and micafungin for all Candida spp. were 0.03/1 μg/mL, 0.06/0.5 μg/mL, and 0.008/1 μg/mL, respectively. CONCLUSION Adequate antifungal therapy and APACHE III score are both independent factors affecting the clinical outcome. The clinical cure rate of the echinocandins group was higher than that of the fluconazole group without significant difference. Although caspofungin had the best clinical cure rate in this study, there was no significant difference between the clinical cure rates among these three echinocandins. All Candida spp. were susceptible in vitro to these three echinocandins.

Comparative antimicrobial susceptibility of aerobic and facultative bacteria from community-acquired bacteremia to ertapenem in Taiwan

BackgroundErtapenem is a once-a-day carbapenem and has excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The susceptibility of isolates of community-acquired bacteremia to ertapenem has not been reported yet. The present study assesses the in vitro activity of ertapenem against aerobic and facultative bacterial pathogens isolated from patients with community-acquired bacteremia by determining and comparing the MICs of cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin. The prevalence of extended broad spectrum β-lactamases (ESBL) producing strains of community-acquired bacteremia and their susceptibility to these antibiotics are investigated.MethodsAerobic and facultative bacteria isolated from blood obtained from hospitalized patients with community-acquired bacteremia within 48 hours of admission between August 1, 2004 and September 30, 2004 in Chang Gung Memorial Hospital at Keelung, Taiwan, were identified using standard procedures. Antimicrobial susceptibility was evaluated by Etest according to the standard guidelines provided by the manufacturer and document M100-S16 Performance Standards of the Clinical Laboratory of Standard Institute. Antimicrobial agents including cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin were used against the bacterial isolates to test their MICs as determined by Etest. For Staphylococcus aureus isolates, MICs of oxacillin were also tested by Etest to differentiate oxacillin-sensitive and oxacillin-resistant S. aureus.ResultsErtapenem was highly active in vitro against many aerobic and facultative bacterial pathogens commonly recovered from patients with community-acquired bacteremia (128/159, 80.5 %). Ertapenem had more potent activity than ceftriaxone, piperacillin-tazobactam, or ciprofloxacin against oxacillin-susceptible S. aureus (17/17, 100%)and was more active than any of these agents against enterobacteriaceae (82/82, 100%).ConclusionBased on the microbiology pattern of community-acquired bacteremia, initial empiric treatment that requires coverage of a broad spectrum of both gram-negative and gram-positive aerobic bacteria, such as ertapenem, may be justified in moderately severe cases of community-acquired bacteremia in non-immunocompromised hosts.